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Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02272946
Recruitment Status : Active, not recruiting
First Posted : October 23, 2014
Last Update Posted : November 10, 2021
Sponsor:
Information provided by (Responsible Party):
Priscilla Hsue, MD, University of California, San Francisco

Tracking Information
First Submitted Date  ICMJE October 13, 2014
First Posted Date  ICMJE October 23, 2014
Last Update Posted Date November 10, 2021
Study Start Date  ICMJE September 2015
Actual Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2014)
  • Number of Adverse Events at week 1 as a measure of safety [ Time Frame: Week 1 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
  • Number of Adverse Events at week 2 as a measure of safety [ Time Frame: Week 2 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
  • Number of Adverse Events at week 4 as a measure of safety [ Time Frame: Week 4 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
  • Number of Adverse Events at week 8 as a measure of safety [ Time Frame: Week 8 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
  • Number of Adverse Events at week 12 as a measure of safety [ Time Frame: Week 12 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
  • Number of Adverse Events at week 18 as a measure of safety [ Time Frame: Week 18 ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
  • Number of Adverse Events at baseline as a measure of safety [ Time Frame: Baseline ]
    Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2014)
  • Change in brachial artery flow-mediated vasodilation (FMD) [ Time Frame: Baseline, 12 weeks ]
    Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter
  • Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT as a measure of vascular inflammation [ Time Frame: Baseline, 12 weeks ]
    Assessed by FDG-PET/CT scanning
  • Rate of change in inflammatory markers of CVD risk [ Time Frame: Baseline, 4 weeks, 12 weeks, 18 weeks ]
    Linear mixed modelling will be used to estimate rates of change over the 18 weeks of treatment. Inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Official Title  ICMJE Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Brief Summary The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 20 individuals will receive a single dose of 150mg canakinumab with follow-up for 18 weeks.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV
  • Cardiovascular Disease
Intervention  ICMJE
  • Drug: Canakinumab
    150mg Canakinumab received subcutaneously
    Other Name: IL--1β
  • Drug: Placebo
    150mg Placebo received subcutaneously
Study Arms  ICMJE
  • Safety Arm
    In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
    Intervention: Drug: Canakinumab
  • Experimental: Canakinumab
    In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.
    Intervention: Drug: Canakinumab
  • Placebo Comparator: Placebo
    In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection
    Intervention: Drug: Placebo
Publications * Kentoffio K, Temu TM, Shakil SS, Zanni MV, Longenecker CT. Cardiovascular disease risk in women living with HIV. Curr Opin HIV AIDS. 2022 Sep 1;17(5):270-278. doi: 10.1097/COH.0000000000000756. Epub 2022 Jul 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 26, 2015)
110
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2014)
20
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. HIV infection,
  2. Age ≥ 40 years < 60 years
  3. On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry
  4. CD4+ T cell count ≥ 400 cells/mm3
  5. HIV RNA level below the standard limit of quantification for 52 weeks prior to entry
  6. High risk for CAD as defined by either documented CVD (including prior MI) or diabetes mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or hsCRP≥2mg/L.)
  7. Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.
  8. Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations

Exclusion Criteria:

  1. Women of childbearing potential or pregnant/nursing women
  2. CABG surgery in the past 3 years
  3. Class IV heart failure
  4. Uncontrolled HTN
  5. History of tuberculosis or latent TB that is not treated
  6. Nephrotic syndrome or eGFR< 30 ml/min/1.73m2
  7. Active hepatic disease or active/chronic hepatitis B or C
  8. Any prior malignancy including KS
  9. Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days
  10. Requirement for live active vaccination 3 months prior to, during, and 3 months after study
  11. Concurrent immune modulating therapy
  12. Diabetes Mellitus
  13. History of multiple imaging studies associated with radiation exposure
  14. Neutropenia defined as ANC<1500/mm
  15. Triglycerides>400 mg/dL
  16. History of hypersensitivity to study drug
  17. History of EBV-related lymphoproliferative disorders
  18. Active or untreated latent TB infection
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 59 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02272946
Other Study ID Numbers  ICMJE Canakinumab
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Priscilla Hsue, MD, University of California, San Francisco
Original Responsible Party University of California, San Francisco
Current Study Sponsor  ICMJE Priscilla Hsue, MD
Original Study Sponsor  ICMJE University of California, San Francisco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Priscilla Hsue, MD University of California, San Francisco
PRS Account University of California, San Francisco
Verification Date November 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP